EP2273987A2 - Filmförmige zubereitung mit öligen substanzen zur oralen verabreichung - Google Patents
Filmförmige zubereitung mit öligen substanzen zur oralen verabreichungInfo
- Publication number
- EP2273987A2 EP2273987A2 EP09745504A EP09745504A EP2273987A2 EP 2273987 A2 EP2273987 A2 EP 2273987A2 EP 09745504 A EP09745504 A EP 09745504A EP 09745504 A EP09745504 A EP 09745504A EP 2273987 A2 EP2273987 A2 EP 2273987A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- preparation
- preparation according
- film
- weight
- oily substance
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 51
- 239000000126 substance Substances 0.000 title claims description 37
- 229920002451 polyvinyl alcohol Polymers 0.000 claims abstract description 44
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims abstract description 33
- 229920000642 polymer Polymers 0.000 claims abstract description 16
- 239000007788 liquid Substances 0.000 claims abstract description 10
- 239000007787 solid Substances 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 4
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 claims description 28
- 229940083037 simethicone Drugs 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 23
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 9
- 239000000796 flavoring agent Substances 0.000 claims description 9
- 239000001525 mentha piperita l. herb oil Substances 0.000 claims description 9
- 239000003921 oil Substances 0.000 claims description 9
- 235000019198 oils Nutrition 0.000 claims description 9
- 235000019477 peppermint oil Nutrition 0.000 claims description 9
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 8
- 240000000467 Carum carvi Species 0.000 claims description 8
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 8
- 240000006927 Foeniculum vulgare Species 0.000 claims description 8
- 229940008099 dimethicone Drugs 0.000 claims description 8
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 8
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims description 8
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 8
- 229940041616 menthol Drugs 0.000 claims description 8
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 8
- 235000005747 Carum carvi Nutrition 0.000 claims description 7
- 235000011173 Foeniculum vulgare subsp piperitum Nutrition 0.000 claims description 7
- 235000002176 Foeniculum vulgare var vulgare Nutrition 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 7
- 238000000576 coating method Methods 0.000 claims description 7
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 6
- 239000010643 fennel seed oil Substances 0.000 claims description 6
- 239000004376 Sucralose Substances 0.000 claims description 5
- 239000011248 coating agent Substances 0.000 claims description 5
- 235000011187 glycerol Nutrition 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 5
- 235000019408 sucralose Nutrition 0.000 claims description 5
- 229920002678 cellulose Polymers 0.000 claims description 4
- 235000010980 cellulose Nutrition 0.000 claims description 4
- 235000019634 flavors Nutrition 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 229920001218 Pullulan Polymers 0.000 claims description 3
- 239000004373 Pullulan Substances 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 230000002026 carminative effect Effects 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 3
- 235000019423 pullulan Nutrition 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 240000003183 Manihot esculenta Species 0.000 claims description 2
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 235000010443 alginic acid Nutrition 0.000 claims description 2
- 229920000615 alginic acid Polymers 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000003125 aqueous solvent Substances 0.000 claims description 2
- 239000000975 dye Substances 0.000 claims description 2
- -1 sorbidex Chemical compound 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims 1
- 239000004094 surface-active agent Substances 0.000 description 9
- 239000000341 volatile oil Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 238000009472 formulation Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 210000004243 sweat Anatomy 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 3
- 235000004357 Mentha x piperita Nutrition 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 235000016257 Mentha pulegium Nutrition 0.000 description 2
- 241001479543 Mentha x piperita Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 235000001050 hortel pimenta Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 239000008385 outer phase Substances 0.000 description 2
- 229920002689 polyvinyl acetate Polymers 0.000 description 2
- 239000011118 polyvinyl acetate Substances 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 235000019613 sensory perceptions of taste Nutrition 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 230000035923 taste sensation Effects 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- NFLGAXVYCFJBMK-RKDXNWHRSA-N (+)-isomenthone Natural products CC(C)[C@H]1CC[C@@H](C)CC1=O NFLGAXVYCFJBMK-RKDXNWHRSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- CSAVDNHVPJNKTC-UHFFFAOYSA-N 5-methyl-2-propan-2-ylcyclohexan-1-ol;5-methyl-2-propan-2-ylphenol;2,2,4-trimethyl-3-oxabicyclo[2.2.2]octane Chemical compound CC(C)C1CCC(C)CC1O.CC(C)C1=CC=C(C)C=C1O.C1CC2CCC1(C)OC2(C)C CSAVDNHVPJNKTC-UHFFFAOYSA-N 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 240000007707 Mentha arvensis Species 0.000 description 1
- 235000018978 Mentha arvensis Nutrition 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- NFLGAXVYCFJBMK-UHFFFAOYSA-N Menthone Chemical compound CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- SJEYSFABYSGQBG-UHFFFAOYSA-M Patent blue Chemical compound [Na+].C1=CC(N(CC)CC)=CC=C1C(C=1C(=CC(=CC=1)S([O-])(=O)=O)S([O-])(=O)=O)=C1C=CC(=[N+](CC)CC)C=C1 SJEYSFABYSGQBG-UHFFFAOYSA-M 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical group CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 208000024330 bloating Diseases 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- JZZIHCLFHIXETF-UHFFFAOYSA-N dimethylsilicon Chemical group C[Si]C JZZIHCLFHIXETF-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- HJUFTIJOISQSKQ-UHFFFAOYSA-N fenoxycarb Chemical compound C1=CC(OCCNC(=O)OCC)=CC=C1OC1=CC=CC=C1 HJUFTIJOISQSKQ-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000008384 inner phase Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229940076522 listerine Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000001771 mentha piperita Substances 0.000 description 1
- 229930007503 menthone Natural products 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229930003647 monocyclic monoterpene Natural products 0.000 description 1
- 150000002767 monocyclic monoterpene derivatives Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000007967 peppermint flavor Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
Definitions
- the present invention relates to solid, film-like preparations with at least one oily substance for oral administration.
- US Patent No. 4,128,445 discloses technical solutions in the loading of carrier material with active ingredients and is based on the subsequent addition of WirkstoffZuritch on prefabricated sheet-like preparations. It describes loading processes in dry and moist form, the aim of a uniform, subsequent distribution of active ingredient on a layer.
- EP 0 219 762 discloses a water-soluble film of starch, gelatin, glycerol or sorbitol, which is coated by roll coating. It will mentions that such dosage forms can also be prepared with flavorings.
- EP 0 460 588 Particular advantages are seen in the composition of 20 to 60 wt .-% film former, 2 to 40 wt .-% gelling agent, 0.1 to 35 wt .-% active or flavoring agent and a maximum of 40 wt .-% of an inert filler.
- a gelling agent is in addition to other compounds
- Aroma-containing sheet-like administration forms for use in the oral area are also known from EP 0 452 446, however, no measures are described as to how a flavoring agent evaporation during production and / or storage can be prevented.
- DE 196 52 257 discloses individually metered, film-shaped
- films of administration that rapidly disintegrate on contact with liquid and can be produced while avoiding losses of active ingredient in their preparation and storage.
- These film-shaped administration forms have an inner, fat-soluble phase in the form of droplets in which the flavoring agent is present and which are distributed in an outer, solid, but water-soluble phase, wherein the outer phase, based on the anhydrous portions, at least 40 wt. % Polyvinyl alcohol, up to 30% by weight a surfactant and 0.1 to 30% by weight of inner phase, based on the outer phase.
- Filmförxnige preparations for use in the mouth are already available commercially as active ingredient or flavoring agent-containing dosage forms.
- wafer-thin strips that leave a cool, breath-fresh taste sensation on the tongue without sucking or chewing in the flavors "Peppermint”, “Wild-Mint” and “Lemon-Frost” by Wrigley under the name ECLIPSE FLASH TM or from Pfizer in the flavors "Cool Mint ® ", “FreshBurst ® ", Cinnamon and "Fresh Citrus” under the brand name Listerine PocketPaks ® offered.
- Hydrophilic film-forming polymers are used for the rapid disintegration or rapid dissolution of film-like formulations upon contact with saliva.
- hydrophilic polymers usually have only a low absorption capacity for lipophilic substances, the amount of oily substance with which hydrophilic films can be loaded is limited. This limitation becomes particularly clear when larger amounts of an oily liquid with a hydrophilic polymer are processed into a film, because this leads to a sweating of the oily substance, for example, through Phase separation during mass production (separation of the O / W emulsion) or later during storage of the films.
- surfactants are commonly added to a mass of hydrophilic polymer and hydrophobic, liquid or oily substance, i. H. Surfactants or emulsifiers that reduce interfacial tension between phases.
- US Pat. No. 6,177,096 discloses the preparation of film-shaped dosage forms with the addition of surfactants.
- the film-forming polymers which are able to stabilize larger amounts of at least one oily substance even without the addition of further surface-active substances, are fully hydrolyzed polyvinyl alcohols and partially hydrolyzed polyvinyl alcohols.
- Polyvinyl alcohols are water-soluble polymers of vinyl alcohol.
- Vinyl alcohol is usually present in the tautomeric form of the acetaldehyde. Therefore, polyvinyl alcohol can not be produced by polymerization of its monomers, but is obtained by saponification of polyvinyl acetate.
- polyvinyl acetate is hydrolyzed or hydrolyzed with sodium hydroxide.
- the polyvinyl alcohols which have not been completely saponified with sodium hydroxide contain vinyl alcohol and vinyl acetate units. These polyvinyl alcohols are referred to as partially hydrolyzed polyvinyl alcohols.
- the enhancement of the surfactant action of other surfactants by polyvinyl alcohol is known.
- Filmbildners is at least 40% (g / g), in each case based on the anhydrous system.
- the water-soluble, solid, film-like preparations according to the invention comprise from 30 to 80% by weight, preferably from 40 to 60% by weight of at least one oily substance and from 5 to 70% by weight, in the preferred embodiment from 5 to 60% by weight. , at least one partially hydrolyzed or fully hydrolyzed polyvinyl alcohol.
- the water-soluble, film-shaped preparation comprises partially hydrolyzed polyvinyl alcohols, in particular partially hydrolyzed polyvinyl alcohols having a degree of hydrolysis of about 88%, that is to say having a degree of hydrolysis of from 86.7 to 88.7%.
- the teilhydrolys faced polyvinyl alcohols have a degree of hydrolysis of about 88%, and a viscosity between 4 and 40 mPa * s as a 4% aqueous solution at 20 0 C.
- particularly preferred partially hydrolyzed polyvinyl alcohols the polyvinyl alcohols available under the trade name Mowiol ® from Kuraray Specialties Europe GmbH Mowiol ® 5-88, Mowiol ® 8-88, Mowiol ® 13-88, Mowiol ® 18-88, Mowiol ® 23 -88, Mowiol ® 26-88 and Mowiol ® 32-88 and similar products are called.
- Suitable oily substances are at room temperature (20 0 C to 23 0 C) and liquid understood difficult or insoluble substances, mixtures of such substances, and such substances with dissolved components in water.
- the oily substances include, for example, compounds such as the fatty oils (glycerol esters of partially unsaturated fatty acids), mineral oils (hydrocarbons obtained predominantly by distillation and refining from petroleum), synthetic oils (synthetically produced oils, eg esters of dicarboxylic acids , Silicone oils) and essential oils (mostly terpenic extracts of plants and parts of plants, and their synthetic copies).
- the oily substances may be pharmaceutically active substances such as dimethicone or simethicone, but the oily substances may also have other functions, for example as a flavoring agent.
- the oily substance is dimethicone or simethicone.
- Dimethicone chemically o (trimethylsilyl) - ⁇ -methylpoly [oxy (dimethylsilylene)]
- Simethicone is silica blended dimethicone. Both are drugs that are used orally as an antifoaming agent to relieve bloating and pain caused by too much gas in the gastrointestinal tract.
- Simethicone is available as a chewable tablet or in liquid form as a medicine.
- Preparations name for the commercially available drugs for example, Elugan ®, Endo-Paractol ®, Espumisan ®, Imogas ®, Lefax ® and simethicone-ratiopharm ®.
- Other oily substances which may be included in the formulation are menthol, bitter fennel oil, peppermint oil, Küznmelöl.
- Peppermint oil (Menthae piperitae aetheroleum) is an essential oil derived from peppermint (Mentha piperita). Peppermint oil is used as a carminative and, because of its digestive and exfoliating properties, is used to treat spasms in the upper gastrointestinal tract and biliary tract.
- the main constituent of peppermint oil is menthol and menthone.
- Menthol is a monocyclic monoterpene alcohol that is poorly soluble in water at 0.4 g / l. at
- menthol is a colorless, crystalline solid.
- Caraway oil (Carvi aetheroleum) is an essential oil derived from the full-ripe fruit of the caraway plant (Carum carvi L.). It is also used as a carminative.
- Bitter fennel oil is an essential oil from the German fennel (Foeniculi amari fructus), which is obtained by steam distillation from the seeds.
- Bitterfat oil has a digestive and antispasmodic effect on the stomach and intestines.
- the preparation according to the invention may consist of from 5 to 70% by weight of at least one partially or fully hydrolyzed polyvinyl alcohol, 30 to 80% by weight of at least one oily substance.
- the proportion of partially and / or fully hydrolyzed polyvinyl alcohol is preferably from 40 to 60% by weight and the proportion of oily substance from 40 to 60% by weight.
- the film-shaped preparation according to the invention based on the dry fraction, consists of 40% by weight of at least one partially or fully hydrolyzed polyvinyl alcohol and 60% by weight of at least one oily substance, preferably dimethicone or simethicone.
- the preparation contains, in addition to dimethicone or simethicone, at least one essential oil from the group comprising peppermint oil, bitter fennel oil and caraway oil.
- the invention is not limited to water-soluble, solid, film-like preparations of at least one polyvinyl alcohol and one or more oily substances.
- the film-like preparation may contain further hydrophilic polymers, even if these films can not be used to produce stable films with an oily substance in large quantities, if only these polymers are used as matrix material and no further surface-active substances are added.
- the additional hydrophilic polymers are preferably selected from the group consisting of cellulose and cellulose derivatives, polyvinylpyrrolidones, polyethylene oxides, pullulan, hydroxypropylated tapioca starch and alginates.
- the additional hydrophilic polymers are selected from the group consisting of hydroxypropylmethylcellulose and sodium carboxymethylcellulose.
- the film-like preparations may contain other auxiliaries or additives.
- the polymer composition for the preparation of the film-shaped preparation Glycerol, sorbidex, sucralose, menthol and / or dyes are added.
- Glycerine 0-20% by weight -%
- Peppermint oil 0-5% by weight
- Caraway oil 0- 5% by weight
- the invention also extends to processes for the preparation of the preparations according to the invention.
- the preparations of the invention can be prepared by a composition comprising at least one fumreliendes polymer from the group of fully and partially hydrolyzed polyvinyl alcohols and at least 30 wt .-%, based on the Dry portion of the preparation, a water-insoluble, oily liquid in an aqueous solvent, preferably water, is produced. With this mass then a pad is coated and dried the resulting coating.
- the filxnförmigen preparations containing as an oily substance dimethicone, simethicone, peppermint oil, bitter fennel oil and / or caraway oil can be used as Carxninativum, because with them complaints in the area of the gastrointestinal tract, such as feeling of fullness, convulsions and / or flatulence treated and alleviated.
- a homogeneous composition of the following composition was prepared:
- a homogeneous composition of the following composition was prepared:
- a homogeneous composition of the following composition was prepared:
- a homogeneous mass of the following composition was prepared: 28% by weight of pullulan (PI-20, viscosity: 128 mm 2 / s) 12% by weight of simethicone 60% by weight of water
- Example 1 Films made from this mass sweat out simethicone. As illustrated in Example 1, it was possible to produce stable films of partially hydrolyzed polyvinyl alcohol which contained a proportion of 60% by weight of simethicone, based on the dry fraction. Stable films could not be produced with other hydrophilic polymers, such as Examples 2 to 8 to be considered as Comparative Examples.
- Exemplary formulation for a stable film with simethicone 27.48% by weight Mowiol 8-88 58.00% by weight simethicone 10.00% by weight peppermint flavor 1.00% by weight sucralose
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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DE102008023345.5A DE102008023345B4 (de) | 2008-05-13 | 2008-05-13 | Filmförmige Zubereitung mit öligen Substanzen zur oralen Verabreichung |
PCT/EP2009/003138 WO2009138170A2 (de) | 2008-05-13 | 2009-04-30 | Filmförmige zubereitung mit öligen substanzen zur oralen verabreichung |
Publications (2)
Publication Number | Publication Date |
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EP2273987A2 true EP2273987A2 (de) | 2011-01-19 |
EP2273987B1 EP2273987B1 (de) | 2013-07-31 |
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EP09745504.2A Active EP2273987B1 (de) | 2008-05-13 | 2009-04-30 | Filmförmige zubereitung mit öligen substanzen zur oralen verabreichung |
Country Status (13)
Country | Link |
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US (1) | US8758803B2 (de) |
EP (1) | EP2273987B1 (de) |
JP (1) | JP5654451B2 (de) |
KR (1) | KR101588479B1 (de) |
CN (1) | CN102026630B (de) |
AU (1) | AU2009248328C1 (de) |
BR (1) | BRPI0907298B8 (de) |
CA (1) | CA2724191C (de) |
DE (1) | DE102008023345B4 (de) |
ES (1) | ES2426963T3 (de) |
MX (1) | MX2010011923A (de) |
WO (1) | WO2009138170A2 (de) |
ZA (1) | ZA201007107B (de) |
Families Citing this family (11)
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US9532952B2 (en) | 2011-01-28 | 2017-01-03 | Physician's Seal, LLC | Controlled-release compositions of melatonin combined with sedative and/or analgesic ingredients |
US8691275B2 (en) | 2011-01-28 | 2014-04-08 | Zx Pharma, Llc | Controlled-release melatonin compositions and related methods |
US8911780B2 (en) | 2011-02-11 | 2014-12-16 | Zx Pharma, Llc | Multiparticulate L-menthol formulations and related methods |
US8808736B2 (en) | 2011-02-11 | 2014-08-19 | Zx Pharma, Llc | Enteric coated multiparticulate controlled release peppermint oil composition and related methods |
TR201808978T4 (tr) | 2011-02-11 | 2018-07-23 | Zx Pharma Llc | Çok partiküllü l-mentol formülasyonları ve ilgili yöntemler. |
DE202011004425U1 (de) * | 2011-03-25 | 2012-03-27 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Zusammensetzung zur Anwendung bei Verdauungsbeschwerden |
KR101787225B1 (ko) | 2013-04-23 | 2017-10-18 | 제트엑스 파마 엘엘씨 | 단백질성 서브코트를 갖는 장용 코팅된 다중 미립자 조성물 |
WO2016015813A1 (de) * | 2014-07-30 | 2016-02-04 | Merck Patent Gmbh | Direkt verpressbare zusammensetzung enthaltend mikrokristalline cellulose |
WO2016015812A1 (de) | 2014-07-30 | 2016-02-04 | Merck Patent Gmbh | Direkt verpressbare polyvinylalkohole |
WO2021090309A1 (en) | 2019-11-04 | 2021-05-14 | Maabarot Products Ltd. | Orally administrable films comprising poorly water soluble active ingredients and preparation thereof |
CN111939332B (zh) * | 2020-08-25 | 2022-07-05 | 深圳市泓云润泽医疗科技有限公司 | 一种在消化道中可溶解的医用材料及其应用 |
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US5001A (en) * | 1847-03-06 | Horse-power | ||
GB1142325A (en) | 1965-05-14 | 1969-02-05 | Higham Stanley Russell | Means for administering drugs |
DE2449865B2 (de) | 1974-10-17 | 1981-06-19 | Schering Ag Berlin Und Bergkamen, 1000 Berlin | Folienförmiges Arzneimittel |
AU514195B2 (en) | 1975-12-15 | 1981-01-29 | F. Hoffmann-La Roche & Co. | Dosage form |
EP0283474A1 (de) | 1985-10-09 | 1988-09-28 | Desitin Arzneimittel GmbH | Verfahren zur herstellung einer darreichungs- und dosierungsform für arzneimittelwirkstoffe, reagentien oder andere wirkstoffe |
WO1991005540A1 (de) | 1989-10-14 | 1991-05-02 | Desitin Arzneimittel Gmbh | Mund- und zahnpflegemittel |
DE4018247A1 (de) | 1990-06-07 | 1991-12-12 | Lohmann Therapie Syst Lts | Herstellungsverfahren fuer schnellzerfallende folienfoermige darreichungsformen |
US5192802A (en) * | 1991-09-25 | 1993-03-09 | Mcneil-Ppc, Inc. | Bioadhesive pharmaceutical carrier |
DE19646392A1 (de) | 1996-11-11 | 1998-05-14 | Lohmann Therapie Syst Lts | Zubereitung zur Anwendung in der Mundhöhle mit einer an der Schleimhaut haftklebenden, Pharmazeutika oder Kosmetika zur dosierten Abgabe enthaltenden Schicht |
DE19652257A1 (de) | 1996-12-16 | 1998-06-18 | Lohmann Therapie Syst Lts | Einzeln dosierte, bei Kontakt mit Flüssigkeit schnell zerfallende, wirkstoff- und insbesondere aromastoffhaltige, folienförmige Darreichnungsform |
US7083781B2 (en) * | 1999-08-19 | 2006-08-01 | Lavipharm S.A. | Film forming polymers, methods of use, and devices and applications thereof |
US20050019291A1 (en) | 2003-07-24 | 2005-01-27 | Yelena Zolotarsky | Emulsion composition of polyvinyl alcohol which forms a peelable film on skin |
AU2006206252B2 (en) * | 2005-01-19 | 2009-11-05 | Neurohealing Pharmaceuticals, Inc. | Methods and compositions for decreasing saliva production |
DE102006003512A1 (de) * | 2006-01-24 | 2007-08-02 | Bayer Schering Pharma Ag | Plättchenförmige Arzneimittel zur transbukkalen Applikation von Arzneistoffen |
JP2010515761A (ja) * | 2007-01-12 | 2010-05-13 | モノソル アールエックス リミテッド ライアビリティ カンパニー | 高用量フィルム組成物およびその製法 |
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2008
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2009
- 2009-04-30 CA CA2724191A patent/CA2724191C/en not_active Expired - Fee Related
- 2009-04-30 KR KR1020107027980A patent/KR101588479B1/ko active IP Right Grant
- 2009-04-30 MX MX2010011923A patent/MX2010011923A/es active IP Right Grant
- 2009-04-30 BR BRPI0907298A patent/BRPI0907298B8/pt not_active IP Right Cessation
- 2009-04-30 CN CN200980116814.9A patent/CN102026630B/zh not_active Expired - Fee Related
- 2009-04-30 JP JP2011508812A patent/JP5654451B2/ja not_active Expired - Fee Related
- 2009-04-30 WO PCT/EP2009/003138 patent/WO2009138170A2/de active Application Filing
- 2009-04-30 AU AU2009248328A patent/AU2009248328C1/en not_active Ceased
- 2009-04-30 US US12/736,521 patent/US8758803B2/en active Active
- 2009-04-30 ES ES09745504T patent/ES2426963T3/es active Active
- 2009-04-30 EP EP09745504.2A patent/EP2273987B1/de active Active
-
2010
- 2010-10-06 ZA ZA2010/07107A patent/ZA201007107B/en unknown
Non-Patent Citations (1)
Title |
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See references of WO2009138170A3 * |
Also Published As
Publication number | Publication date |
---|---|
CN102026630B (zh) | 2015-11-25 |
JP5654451B2 (ja) | 2015-01-14 |
US8758803B2 (en) | 2014-06-24 |
BRPI0907298B1 (pt) | 2019-05-28 |
DE102008023345A1 (de) | 2009-11-19 |
MX2010011923A (es) | 2010-11-30 |
DE102008023345B4 (de) | 2014-12-04 |
CA2724191C (en) | 2016-05-24 |
KR101588479B1 (ko) | 2016-01-25 |
ES2426963T3 (es) | 2013-10-28 |
AU2009248328C1 (en) | 2015-05-07 |
EP2273987B1 (de) | 2013-07-31 |
AU2009248328B2 (en) | 2014-10-23 |
WO2009138170A2 (de) | 2009-11-19 |
WO2009138170A3 (de) | 2010-03-18 |
AU2009248328A1 (en) | 2009-11-19 |
CN102026630A (zh) | 2011-04-20 |
KR20110009700A (ko) | 2011-01-28 |
CA2724191A1 (en) | 2009-11-19 |
JP2011520818A (ja) | 2011-07-21 |
AU2009248328B9 (en) | 2014-11-20 |
BRPI0907298A2 (pt) | 2016-07-05 |
BRPI0907298B8 (pt) | 2021-05-25 |
ZA201007107B (en) | 2011-05-25 |
US20110064830A1 (en) | 2011-03-17 |
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